Combination of cyst fluid CEA and CA 125 is an accurate diagnostic tool for differentiating mucinous cystic neoplasms from intraductal papillary mucinous neoplasms

Background/objectivesDespite advances in imaging techniques, diagnosis and management of pancreatic cystic lesions still remains challenging. The objective of this study was to determine the utility of cyst fluid analysis (CEA, CA 19-9, CA 125, amylase, and cytology) in categorizing pancreatic cystic lesions, and in differentiating malignant from benign cystic lesions.MethodsA retrospective analysis of 68 patients with histologically and clinically confirmed cystic lesions was performed. Cyst fluid was obtained by surgical resection (n = 45) or endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) (n = 23). Cyst fluid tumor markers and amylase were measured and compared between the cyst types.ResultsReceiver operating characteristic (ROC) curve analysis of the tumor markers demonstrated that cyst fluid CEA provided the greatest area under ROC curve (AUC) (0.884) for differentiating mucinous versus non-mucinous cystic lesions. When a CEA cutoff value was set at 67.3 ng/ml, the sensitivity, specificity and accuracy for diagnosing mucinous cysts were 89.2%, 77.8%, and 84.4%, respectively. The combination of cyst fluid CEA content >67.3 ng/ml and cyst fluid CA 125 content >10.0 U/ml segregated 77.8% (14/18) of mucinous cystic neoplasms (MCNs) from other cyst subtypes. On the other hand, no fluid marker was useful for differentiating malignant versus benign cystic lesions. Although cytology (accuracy 83.3%) more accurately diagnosed malignant cysts than CEA (accuracy 65.6%), it lacked sensitivity (35.3%).ConclusionsOur results demonstrate that cyst fluid CEA can be a helpful marker in differentiating mucinous from non-mucinous, but not malignant from benign cystic lesions. A combined CEA and CA 125 approach may help segregate MCNs from IPMNs.     

Mucinous cystic neoplasm of the pancreas: Is surgical resection recommended for all surgically fit patients?

BackgroundSurgical removal of mucinous cystic neoplasms (MCNs) is usually recommended because of the risk of malignancy. However, increased experience of MCNs suggests that the incidence of invasion is lower than had been thought. This study was designed to establish more reasonable surgical indications for MCN through re-assessment using strict pathologic diagnostic criteria.MethodsNinety-four patients who underwent surgical removal of MCNs at Seoul National University Hospital from 1991 to 2012 were retrospectively analyzed. Pathologic results were re-evaluated by an experienced pathologist. Medical records and radiologic images were reviewed to determine factors predicting malignancy.ResultsOf the 94 patients, 4 were found to have intraductal papillary mucinous neoplasms (IPMNs). Of the 90 MCNs, 60 (66.7%) were low-grade, 21 (23.3%) were intermediate-grade, and 5 (5.5%) were high-grade dysplasias; and 4 (4.4%) were invasive carcinoma. Mural nodules on CT scan (p = 0.005) and abnormal serum CA19-9 concentration (p = 0.029) were significant predictors of malignancy. All MCNs less than 3 cm in size with normal serum tumor markers were benign and all malignant MCNs had cyst fluid CA19-9 over 10,000 units/ml. The five year disease specific survival rates were 98.8% for all patients and 75.0% for those with invasive MCNs.ConclusionMCNs had a low prevalence of malignancy. Regardless of the histological grade, long-term outcome was excellent. Therefore, in the absence of specific symptoms, surgery may not be indicated for MCNs <3 cm without mural nodules or elevated serum tumor markers. Validation by a prospective study with very careful design is needed.     

Pancreatic incidentalomas: Investigation and management

The incidence of pancreatic incidentalomas (PIs) detected in otherwise asymptomatic patients is growing with the increasing quality and use of advanced imaging techniques. PI can present as isolated main pancreatic duct dilation or as a solid or cystic lesion. Although historically thought to be relatively rare, PIs are rather common, particularly cystic lesions of the pancreas, which can be detected in up to 49% of the general population. With the poor prognosis of pancreatic cancer, PIs are an opportunity for prevention and early diagnosis, but when managed poorly, they can also lead to overtreatment and unnecessary morbidity. The management of PI should begin with a dedicated pancreas protocol computed tomography (CT) scan or magnetic resonance imaging (MRI) to accurately characterize duct size, lesion characteristics and establish an accurate baseline for subsequent follow up. Diagnosis and subsequent management depends on the extent of main duct dilation and solid versus cystic appearance. Solid lesions are highly concerning for malignancy. Cystic lesions can be further categorized as intraductal papillary mucinous neoplasms of the pancreas (IPMNs) or mucinous cystic neoplasms (MCNs), both of which harbour malignant potential, or as serous cystic neoplasms (SCNs) that are benign. In this paper, we summarize the major challenges related to PI and present pragmatic suggestions for management.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Decision making for pancreatic resection in patients with intraductal papillary mucinous neoplasms

AIM: To identify a practical approach for preoperative decision-making in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: Between March 1999 and November 2006, the clinical characteristics, pathological data and computed tomography/magnetic resonance imaging (CT/MRI) of 54 IPMNs cases were retrieved and analyzed. The relationships between the above data and decision-making for pancreatic resection were analyzed using SPSS 13.0 software. Univariate analysis of risk factors for malignant or invasive IPMNs was performed with regard to the following variables: carcinoembryonic antigen, carbohydrate antigen 19-9 (CA19-9) and the characteristics from CT/MRI images. Receiver operating characteristic (ROC) curve analysis for pancreatic resection was performed using significant factors from the univariate analysis. RESULTS: CT/MRI images, including main and mixed duct IPMNs, tumor size > 30 mm or a solid component appearance in the lesion, and preoperative serum CA19-9 > 37 U/mL had good predictive value for determining pancreatic resection (P < 0.05), but with limitations. Combining the above factors (CT/MRI images and CA19-9) improved the accuracy and sensitivity for determining pancreatic resection in IPMNs. Using ROC analysis, the area under the curve reached 0.893 (P<0.01, 95%CI: 0.763-1.023), with a sensitivity, specificity, positive predictive value and negative predictive value of 95.2%, 83.3%, 95.2% and 83.3%, respectively. CONCLUSION: Combining preoperative CT/MRI images and CA19-9 level may provide useful information for surgical decision-making in IPMNs.     

Prognostic Significance of the Labeling of Adnab-9 in Pancreatic Intraductal Papillary Mucinous Neoplasms

Summary Background. Pancreatic intraductal papillary mucinous neoplasms (IPMN), morphologically resembling colonic adenomas, often have an indefinable malignant potential. We used a monoclonal antibody (MAb) raised against colonic adenomas, Adnab-9, to identify patients with a better prognosis. Methods. We assessed Adnab-9-labeled sections of these neoplasms from 50 patients, 13 pancreatic adenocarcinomas, and 32 colonic adenomas using standard immunohistochemical techniques. Results. 26% of the IPMNs labeled with Adnab-9 as compared to 0% of pancreatic ductal cancers or surrounding benign tissues, (p<0.001) and 53% of adenomas (p<0.025). Labeling in IPMNs was usually seen in the noninvasive epithelium suggesting that Adnab-9 is a premalignant marker in these lesions. Labeling of invasive IPMN’s identified a group of patients with a superior overall survival (p=0.027). Conclusion. Adnab-9 labeling-characteristics appear similar for both IPMNs and adenomatous polyps, suggesting that they are analogous lesions. Adnab-9 labeling may also be a useful prognostic marker for invasive intraductal papillary mucinous neoplasms.     

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis

BackgroundFucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA.MethodsPhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA.ResultsThe sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA.ConclusionPhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.     

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors,i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian‐type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low‐grade PanINs. Mucin expression profiles suggest intestinal‐type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB‐type IPMNs progress toward ductal adenocarcinoma. It is a well‐described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step‐wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.     

Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study

BACKGROUND & AIMS: Cysts of the pancreas display a wide spectrum of histology, including inflammatory (pseudocysts), benign (serous), premalignant (mucinous), and malignant (mucinous) lesions. Endoscopic ultrasonography (EUS) may offer a diagnostic tool through the combination of imaging and guided, fine-needle aspiration (FNA). The purpose of this investigation was to determine the most accurate test for differentiating mucinous from nonmucinous cystic lesions. METHODS: The results of EUS imaging, cyst fluid cytology, and cyst fluid tumor markers (CEA, CA 72-4, CA 125, CA 19-9, and CA 15-3) were prospectively collected and compared in a multicenter study using histology as the final diagnostic standard. RESULTS: Three hundred forty-one (341) patients underwent EUS and FNA of a pancreatic cystic lesion; 112 of these patients underwent surgical resection, providing a histologic diagnosis of the cystic lesion (68 mucinous, 7 serous, 27 inflammatory, 5 endocrine, and 5 other). Receiver operator curve analysis of the tumor markers demonstrated that cyst fluid CEA (optimal cutoff of 192 ng/mL) demonstrated the greatest area under the curve (0.79) for differentiating mucinous vs. nonmucinous cystic lesions. The accuracy of CEA (88 of 111, 79%) was significantly greater than the accuracy of EUS morphology (57 of 112, 51%) or cytology (64 of 109, 59%) (P < 0.05). There was no combination of tests that provided greater accuracy than CEA alone (P < 0.0001). CONCLUSIONS: Of tested markers, cyst fluid CEA is the most accurate test available for the diagnosis of mucinous cystic lesions of the pancreas.     

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillary-mucinous tumors

Background/Purpose. The number of patients with cystic neoplasms of the pancreas as detected using various types of imaging techniques has been steadily increasing. Among the cystic neoplasms, mucinous cystic neoplasms (MCNs) and intraductal papillary-mucinous tumors (IPMTs) were comparatively more frequently encountered. We used imaging techniques to focus on the differential diagnosis of MCNs and IPMTs, and tumor staging.Methods. Fifteen patients with MCNs with ovarian-like stroma and 109 patients with IPMTs were experienced. We examined the image findings for the differential diagnosis and stage diagnosis of these two types of cystic neoplasms.Results. Endoscopic ultrasonography could reveal detailed images of internal structure and was effective for the diagnosis of MCNs. Other endoscopic imaging modalities could not give specific findings for MCNs. Endoscopic retrograde cholangiopancreatography (ERCP; including duodenoscopic findings and pancreatogram) and pancreatoscopy showed the characteristic and specific findings of IPMTs. Also, endoscopic ultrasonography and intraductal ultrasonography were found to have high sensitivity and diagnostic accuracy for their differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive lesions in IPMTs.Conclusions. Endoscopic imaging techniques are capable of revealing the detailed structure of pancreatic cystic lesions. They are effective for differential diagnosis, for assessing the degree of malignancy, and for deciding upon an appropriate treatment in patients with IPMTs.     

Whole-exome sequencing of neoplastic cysts of the pancreas reveals recurrent mutations in components of ubiquitin-dependent pathways

More than 2% of adults harbor a pancreatic cyst, a subset of which progresses to invasive lesions with lethal consequences. To assess the genomic landscapes of neoplastic cysts of the pancreas, we determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts of each of the major neoplastic cyst types: serous cystadenomas (SCAs), intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasms (MCNs), and solid pseudopapillary neoplasms (SPNs). SPNs are low-grade malignancies, and IPMNs and MCNs, but not SCAs, have the capacity to progress to cancer. We found that SCAs, IPMNs, MCNs, and SPNs contained 10 ± 4.6, 27 ± 12, 16 ± 7.6, and 2.9 ± 2.1 somatic mutations per tumor, respectively. Among the mutations identified, E3 ubiquitin ligase components were of particular note. Four of the eight SCAs contained mutations of the von Hippel-Lindau gene (VHL), a key component of the VHL ubiquitin ligase complex that has previously been associated with renal cell carcinomas, SCAs, and other neoplasms. Six of the eight IPMNs and three of the eight MCNs harbored mutations of RNF43, a gene coding for a protein with intrinsic E3 ubiquitin ligase activity that has not previously been found to be genetically altered in any human cancer. The preponderance of inactivating mutations in RNF43 unequivocally establish it as a suppressor of both IPMNs and MCNs. SPNs contained remarkably few genetic alterations but always contained mutations of CTNNB1, previously demonstrated to inhibit degradation of the encoded protein (β-catenin) by E3 ubiquitin ligases. These results highlight the essential role of ubiquitin ligases in these neoplasms and have important implications for the diagnosis and treatment of patients with cystic tumors.     

胰腺导管内乳头状黏液瘤的研究进展

胰腺导管内乳头状黏液瘤(intraductal papillary mucinous neoplasm,IPMNs)为来源于胰腺导管上皮的分化程度多样的胰腺肿瘤,位于主胰管或其分支内,可分泌黏液,为胰腺癌的癌前病变.区分IPMNs的良恶性对制定治疗方案,预估患者预后意义重大.随影像学和内镜的发展,IPMNs发现率逐年提...     

Imaging features of intraductal papillary mucinous neoplasms of the pancreas in multi-detector row computed tomography

AIM： To retrospectively evaluate the imaging features of pancreatic intraductal papillary mucinous neoplasms （IPMNs） in multi-detector row computed tomography （MDCT）.
METHODS： A total of 20 patients with pathologicallyconfirmed intraductal papillary mucinous neoplasms （IPMNs） were included in this study. Axial MDCT images combined with CT angiography （CTA） and multiplanar volume reformations （MPVR） or curved reformations （CR） were preoperatively acquired. Two radiologists （Tan L and Wang DB） reviewed all the images in consensus using an interactive picture archiving and communication system. The disputes in readings were resolved through consultation with a third experienced radiologist （Chen KM）. Finally, the findings and diagnoses were compared with the pathologic results.
RESULTS： The pathological study revealed 12 malignant IPMNs and eight benign IPMNs. The diameters of the cystic lesions and main pancreatic ducts （MPDs） were significantly larger in malignant IPMNs compared with those of the benign IPMNs （P 〈 0.05）. The combinedtype IPMNs had a higher rate of malignancy than the other two types of IPMNs （P 〈 0.05）. Tumors with mural nodules and thick septa had a significantly higher incidence of malignancy than tumors without these features （P 〈 0.05）. Communication of side-branch IPMNs with the MPD was present in nine cases at pathologic examination. Seven of them were identified from CTA and MPVR or CR images. From comparison with the pathological diagnosis, the sensitivity, specificity, and accuracy of MDCT in characterizing the malignancy of IPMN of the pancreas were determined to be 100%, 87.5% and 95%, respectively.
CONCLUSION： MDCT with CTA and MPVR or CR techniques can elucidate the imaging features of IPMNs and help predict the malignancy of these tumors.     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas （IPMNs）. IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ＂new＂ but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head （75%） while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-year- old male diagnosed with IPMN （carcinoma in situ） in the pancreatic head and a branch duct type IPMN （duct atypia） in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.     

Diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs: A systematic review and meta-analysis

ObjectivesDifferential diagnosis of malignant and benign intraductal papillary mucinous neoplasms (IPMNs) is essential to determine the optimal treatment. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently used to diagnose pancreatic cystic lesions worldwide, but few studies have focused on the diagnostic yield to distinguish malignant and benign IPMNs. Therefore, we aim to systematically review the diagnostic yield of EUS-FNA-based cytology to distinguish malignant and benign IPMNs.MethodsRelevant studies with a reference standard of definitive surgical histology which published between 2002 and 2012 were identified via MEDLINE and SCOPUS. Malignant IPMNs included invasive adenocarcinoma, carcinoma in situ, and high-grade dysplasia.ResultsFour studies with 96 patients were included in this meta-analysis. For diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs, the pooled sensitivity and specificity were 64.8% (95% CI, 0.44–0.82) and 90.6% (95% CI, 0.81–0.96), respectively. Similarly, the positive likelihood ratio and negative likelihood ratio were 6.35 (95% CI, 2.95–13.68) and 0.43 (95% CI, 0.14–1.34), respectively. Malignant IPMNs were observed in 20.8% (20/96) of patients in EUS-FNA studies.ConclusionsEUS-FNA-based cytology has good specificity but poor sensitivity in differentiating benign from malignant IPMNs. Newer techniques or markers are needed to improve diagnostic yield.     

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.     

Intraductal papillary mucinous neoplasms of the pancreas: an analysis of protein expression and clinical features

Background/Purpose

The molecular pathology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas has not been well characterized, and there are no reliable markers to predict the presence of associated invasive carcinoma in patients with IPMNs. We investigated the clinicopathologic characteristics of 37 IPMNs and the immunohistochemical findings of these tumors to investigate the malignancy of IPMNs.

Methods

Between May 1992 and September 2003, 37 patients with IPMNs, 24 with adenoma and 13 with carcinoma, underwent pancreatic resections at Sapporo Medical University Hospital, Japan. In tumor specimens from these patients, we immunohistochemically analyzed the expression of p53 protein, proliferating-cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), matrix metalloproteinase-7 (MMP-7), and E-cadherin. Clinical features and follow-up after resection were recorded.

Results

Aberrant expression of the proteins examined was frequently observed. Namely, there were significant differences in the expression of MMP-7 according to clinicopathological characteristics. Positive expression of MMP-7 was found in all of nine patients with infiltrating ductal pancreatic adenocarcinoma (IDC) and in all of seven patients with invasive intraductal papillary mucinous adenocarcinoma (IC-IPMC); however, 33.3% of patients with noninvasive IPMA, 58.3% of patients with intraductal papillary mucinous adenoma (IPMA), and all normal pancreatic tissues were negative for MMP-7; differences which were statistically significant (P < 0.05).

Conclusions

Our current results indicate that MMP-7 may play a significant role in the progression of noninvasive to invasive IPMC.     

Diagnostic role and prognostic value of tumor markers in high-grade gastro-enteropancreatic neuroendocrine neoplasms

ObjectivesHigh-grade gastro-enteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of rare tumors of two different types: well differentiated neuroendocrine tumors grade 3 (NETs G3) and poorly differentiated neuroendocrine carcinomas (NECs). This study aimed to explore the value of eight common preoperative markers in differentiating NETs G3 from NECs and the prognosis prediction of high-grade GEP-NENs.MethodsSeventy-two patients diagnosed with high-grade GEP-NENs who underwent surgery at our institution were recruited for this study. Demographic and clinicopathological characteristics, preoperative serum tumor markers, and survival data were collected and analyzed. Kaplan–Meier methods were used to analyze survival rates, and a Cox regression model was used to perform multivariate analyses.ResultsSerum carcinoembryonic antigen (CEA) was dramatically higher in NECs than in NETs G3 (P = 0.025). After follow-up, 57 of the 72 patients remained for survival analysis. Elevated serum carbohydrate antigen 19-9 (CA19-9), CEA, cancer antigen 125 and sialic acid (SA) levels indicated poorer survival of high-grade GEP-NEN patients. Only CA19-9 (HR: 6.901, 95% CI: 1.843 to 25.837, P = 0.004) was regarded as an independent risk factor for overall survival. Serum CA19-9 (HR: 4.689, 95% CI: 1.127 to 19.506, P = 0.034) was also regarded as an independent factor for overall survival in NECs.ConclusionsSerum CEA levels can be used to distinguish NETs G3 from NECs. Preoperative CA19-9, CEA, cancer antigen 125 and SA levels have predictive value in the prognosis of high-grade GEP-NENs. Preoperative CA19-9, neuron-specific enolase, and SA levels can predict the prognosis of NECs.